Diagnostic and Therapeutic Approaches in Periodontology: From Traditional Concepts to Modern Innovations

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Congratulations on the job you have done and presented in this manuscript. I believe that your work is significant, highly relevant and fits the scope of the journal. However, for the moment there are multiple issues that need to be addressed prior to consideration for publication in a such high quality journal.

1. The methodology is by far the weakest part of the manuscript: although the introduction states that a narrative review was performed, nothing is stated about: exact search string, MeSH terms,date of search, number of retrieved studies, inclusion/exclusion criteria, study selection process...
2. The other main concern is related to the discussion section: insufficient discussion on biomarkers( there is no reproductibility, no external validation,sensitivity, heterocenicity between the studies). Furthermore, there is a limited discussion regarding therapeuthic interventions like: regenerative aproaches,host modulation, biomaterials, minimally invasive surgery.
3. Table 1 could be improved: rather that only listing biomarkers I would add evidence level; advantages/disadvantages; limitations
4. Minor concerns: some subsection numbering appears inconsistent: subsection 1 is followed by subsection 2.1;Some abbreviations appear before being defined; the introduction in my opinion is very long. 

Author Response

Response to Reviewers

Dear Editor and Reviewers,

We sincerely thank the reviewers for their careful and constructive evaluation of our manuscript. The comments have substantially improved the clarity, rigor, and readability of the work. Below, we address each point individually; reviewer comments are in italics, and our responses follow. All changes are highlighted in the revised manuscript.

Reviewer 1

Comment 1. The methodology is the weakest part: no exact search string, MeSH terms, date of search, number of retrieved studies, inclusion/exclusion criteria, or study selection process.

We restructured the Materials and Methods into five subsections following the SANRA framework: Study Design and Reporting Framework (2.1), Data Sources and Search Strategy (2.2), Eligibility Criteria (2.3), Study Selection (2.4), and Quality Appraisal and Evidence Synthesis (2.5). We now report the databases searched (PubMed/MEDLINE, Scopus, Web of Science), the period covered (January 2015–December 2025), the last search-update date (20 January 2026), the combination of MeSH and free-text terms with Boolean operators, and representative search strings, together with explicit inclusion and exclusion criteria and the screening/selection process. We also added the number of records identified and screened at each stage to §2.4 The final synthesis included 66 references.

Comment 2. Insufficient discussion of biomarkers (reproducibility, external validation, sensitivity, heterogeneity) and limited discussion of therapeutic interventions (regenerative approaches, host modulation, biomaterials, minimally invasive surgery).

We expanded the critical discussion of biomarkers throughout Sections 3.5 and 5, explicitly addressing reproducibility, the frequent absence of external validation, reported sensitivity/specificity, and between-study heterogeneity, and clarifying that cross-sectional discrimination does not equate to validated prediction of activity or progression. Section 7 (Therapeutic Implications) was reorganized into dedicated subsections covering host- and microbiome-directed adjuncts (7.2), regeneration and minimally invasive surgery (7.3), and biomaterials and advanced delivery systems (7.4), each distinguishing clinically validated interventions from investigational ones.

Comment 3. Table 1 could be improved by adding evidence level, advantages/disadvantages, and limitations.

Table 1 was restructured to include, for each omics approach, columns for representative evidence, level of evidence, advantages, and limitations/disadvantages. The caption, the introductory sentence, and the table note were updated accordingly.

Comment 4. Minor: inconsistent subsection numbering (section 1 followed by 2.1); some abbreviations used before being defined; the introduction is very long.

Subsection numbering was made consistent throughout; in particular, the subsections of Section 7 were renumbered 7.1–7.5. Abbreviations are now defined at first use, including cone-beam computed tomography (CBCT), European Federation of Periodontology (EFP), and matrix metalloproteinase (MMP). The Introduction was condensed to focus on the rationale and aims of the review.

Reviewer 2

Comment 1. The manuscript lacks a clear structure for a narrative review; the SANRA checklist should be followed.

The manuscript was restructured according to SANRA (cited as reference 1), which now guides the justification of importance, the statement of aims, the description of the literature search, referencing, scientific reasoning, and the presentation of relevant data. This allowed us to trim the text and analyze the available data more critically.

Comment 2. The study is not easy to follow; data of the studies are not reported and not critically analyzed.

We revised the text to report quantitative findings (e.g., diagnostic AUCs, sensitivity/specificity) and to interpret rather than merely summarize them, consistently emphasizing validation status, heterogeneity, and clinical applicability across the diagnostic domains.

Comment 3. The data of the included studies should be presented as a table.

Study-level data are now presented in Table 1 (omics-based approaches) and Table 2 (biological-fluid biomarkers), each reporting representative evidence, performance, and limitations.

Comment 4. Adding figures would help present each section (e.g., a figure for CBCT, a figure for AI).

We added two new figures: Figure 2 (clinical indications and translational requirements of CBCT) and Figure 3 (biological fluids and biomarkers: scope, representative markers, and interpretation), complementing the existing Figure 1 on the roles of digital imaging and AI. Each is placed within the relevant section.

Comment 5. A graphical abstract needs to be added.

An original graphical abstract summarizing the transition from traditional concepts to precision periodontology has been added after the keywords and is provided as a separate file, prepared in accordance with MDPI's specifications.

Reviewer 3

Comment 1. The manuscript is excessively long and repetitive.

We condensed the text and removed redundant background, merging overlapping content (particularly across biomarkers, omics, microbiome, and predictive models) to reduce repetition while preserving the key scientific messages.

Comment 2. The review lacks sufficient critical analysis.

Throughout the revision, we shifted from description to interpretation, comparing the strengths and limitations of the different diagnostic technologies, their current level of evidence, clinical applicability, and remaining challenges. Table 1 now makes the level of evidence explicit.

Comment 3. The methodology of the literature review should be strengthened.

As detailed in our response to Reviewer 1 (Comment 1), the methodology now explains how studies were identified and selected, the eligibility criteria applied, how quality was appraised, and how the evidence was synthesized.

Comment 4. Clinical applicability should be emphasized; distinguish routine tools from experimental ones.

The revised text and tables consistently distinguish technologies currently available for routine clinical use from those that remain experimental or require further validation, and the added figures and graphical abstract reinforce this distinction (foundation vs. adjunct vs. investigational).

Comment 5. The manuscript would benefit from improved organization; some chapters overlap and could be merged.

Overlapping sections were consolidated and reordered to improve logical flow, following the thematic structure described in §2.5.

Minor comments. Repeated citations were reduced; long sentences were shortened; tables were revised to complement rather than duplicate the text; the English was professionally edited for style and consistency; and the Conclusions were rebalanced to present both the promise of emerging technologies and the barriers (validation, standardization, cost, and accessibility) that currently limit their routine implementation.

We believe these revisions address all the reviewers' concerns and hope the manuscript is now suitable for publication. We thank the reviewers again for their valuable input.

Sincerely,
The Authors

Reviewer 2 Report

Comments and Suggestions for Authors

Review for the Manuscript ID: biomedicines-4492121 entitled “Diagnostic and Therapeutic Approaches in Periodontology: From Traditional Concepts to Modern Innovations”

 

I think the manuscript comprehensively reviewed the current status of periodontal diagnosis and therapies, however, there are some points need to be addressed as follow:

1. The manuscript lack a clear structure for writing narrative review. SANRA check list for writing narrative review should be followed as provided below. Having done that, the manuscript would be trimmed and critically analyze the available data.

https://link.springer.com/article/10.1186/s41073-019-0064-8

2. 2. Again, there is not clear structure and the study is not easy to follow, for example, data of the studies are not reported and not critically analyzed.
3. The data of those studies included should be presented as table.
4. I think adding some figures would be better to present all the writing and briefly present each section such as a figure for CBCT, a figure of AI …etc.
5. A graphical abstract need to be added too.

 

BW, 

Author Response

Response to Reviewers

Dear Editor and Reviewers,

We sincerely thank the reviewers for their careful and constructive evaluation of our manuscript. The comments have substantially improved the clarity, rigor, and readability of the work. Below, we address each point individually; reviewer comments are in italics, and our responses follow. All changes are highlighted in the revised manuscript.

Reviewer 1

Comment 1. The methodology is the weakest part: no exact search string, MeSH terms, date of search, number of retrieved studies, inclusion/exclusion criteria, or study selection process.

We restructured the Materials and Methods into five subsections following the SANRA framework: Study Design and Reporting Framework (2.1), Data Sources and Search Strategy (2.2), Eligibility Criteria (2.3), Study Selection (2.4), and Quality Appraisal and Evidence Synthesis (2.5). We now report the databases searched (PubMed/MEDLINE, Scopus, Web of Science), the period covered (January 2015–December 2025), the last search-update date (20 January 2026), the combination of MeSH and free-text terms with Boolean operators, and representative search strings, together with explicit inclusion and exclusion criteria and the screening/selection process. We also added the number of records identified and screened at each stage to §2.4 The final synthesis included 66 references.

Comment 2. Insufficient discussion of biomarkers (reproducibility, external validation, sensitivity, heterogeneity) and limited discussion of therapeutic interventions (regenerative approaches, host modulation, biomaterials, minimally invasive surgery).

We expanded the critical discussion of biomarkers throughout Sections 3.5 and 5, explicitly addressing reproducibility, the frequent absence of external validation, reported sensitivity/specificity, and between-study heterogeneity, and clarifying that cross-sectional discrimination does not equate to validated prediction of activity or progression. Section 7 (Therapeutic Implications) was reorganized into dedicated subsections covering host- and microbiome-directed adjuncts (7.2), regeneration and minimally invasive surgery (7.3), and biomaterials and advanced delivery systems (7.4), each distinguishing clinically validated interventions from investigational ones.

Comment 3. Table 1 could be improved by adding evidence level, advantages/disadvantages, and limitations.

Table 1 was restructured to include, for each omics approach, columns for representative evidence, level of evidence, advantages, and limitations/disadvantages. The caption, the introductory sentence, and the table note were updated accordingly.

Comment 4. Minor: inconsistent subsection numbering (section 1 followed by 2.1); some abbreviations used before being defined; the introduction is very long.

Subsection numbering was made consistent throughout; in particular, the subsections of Section 7 were renumbered 7.1–7.5. Abbreviations are now defined at first use, including cone-beam computed tomography (CBCT), European Federation of Periodontology (EFP), and matrix metalloproteinase (MMP). The Introduction was condensed to focus on the rationale and aims of the review.

Reviewer 2

Comment 1. The manuscript lacks a clear structure for a narrative review; the SANRA checklist should be followed.

The manuscript was restructured according to SANRA (cited as reference 1), which now guides the justification of importance, the statement of aims, the description of the literature search, referencing, scientific reasoning, and the presentation of relevant data. This allowed us to trim the text and analyze the available data more critically.

Comment 2. The study is not easy to follow; data of the studies are not reported and not critically analyzed.

We revised the text to report quantitative findings (e.g., diagnostic AUCs, sensitivity/specificity) and to interpret rather than merely summarize them, consistently emphasizing validation status, heterogeneity, and clinical applicability across the diagnostic domains.

Comment 3. The data of the included studies should be presented as a table.

Study-level data are now presented in Table 1 (omics-based approaches) and Table 2 (biological-fluid biomarkers), each reporting representative evidence, performance, and limitations.

Comment 4. Adding figures would help present each section (e.g., a figure for CBCT, a figure for AI).

We added two new figures: Figure 2 (clinical indications and translational requirements of CBCT) and Figure 3 (biological fluids and biomarkers: scope, representative markers, and interpretation), complementing the existing Figure 1 on the roles of digital imaging and AI. Each is placed within the relevant section.

Comment 5. A graphical abstract needs to be added.

An original graphical abstract summarizing the transition from traditional concepts to precision periodontology has been added after the keywords and is provided as a separate file, prepared in accordance with MDPI's specifications.

Reviewer 3

Comment 1. The manuscript is excessively long and repetitive.

We condensed the text and removed redundant background, merging overlapping content (particularly across biomarkers, omics, microbiome, and predictive models) to reduce repetition while preserving the key scientific messages.

Comment 2. The review lacks sufficient critical analysis.

Throughout the revision, we shifted from description to interpretation, comparing the strengths and limitations of the different diagnostic technologies, their current level of evidence, clinical applicability, and remaining challenges. Table 1 now makes the level of evidence explicit.

Comment 3. The methodology of the literature review should be strengthened.

As detailed in our response to Reviewer 1 (Comment 1), the methodology now explains how studies were identified and selected, the eligibility criteria applied, how quality was appraised, and how the evidence was synthesized.

Comment 4. Clinical applicability should be emphasized; distinguish routine tools from experimental ones.

The revised text and tables consistently distinguish technologies currently available for routine clinical use from those that remain experimental or require further validation, and the added figures and graphical abstract reinforce this distinction (foundation vs. adjunct vs. investigational).

Comment 5. The manuscript would benefit from improved organization; some chapters overlap and could be merged.

Overlapping sections were consolidated and reordered to improve logical flow, following the thematic structure described in §2.5.

Minor comments. Repeated citations were reduced; long sentences were shortened; tables were revised to complement rather than duplicate the text; the English was professionally edited for style and consistency; and the Conclusions were rebalanced to present both the promise of emerging technologies and the barriers (validation, standardization, cost, and accessibility) that currently limit their routine implementation.

We believe these revisions address all the reviewers' concerns and hope the manuscript is now suitable for publication. We thank the reviewers again for their valuable input.

Sincerely,
The Authors

Reviewer 3 Report

Comments and Suggestions for Authors

I believe that the manuscript addresses an important and timely topic and provides a broad overview of current developments in periodontal diagnostics and therapy. However, in its current form, it requires major revision before it can be considered for publication. The review is comprehensive but suffers from significant structural, methodological, and scientific weaknesses that limit its impact and readability.

Major comments

1. The manuscript is excessively long and repetitive.

Several sections provide extensive background information that is already well established in the literature. Many concepts are described repeatedly (e.g., conventional periodontal diagnosis, biomarkers, AI applications), making the manuscript unnecessarily lengthy. The text should be substantially condensed to improve readability while maintaining the key scientific messages.

1. The review lacks sufficient critical analysis.

Although numerous studies are cited, the manuscript mainly summarizes published findings without critically comparing the available evidence. Greater emphasis should be placed on discussing the strengths and limitations of different diagnostic technologies, their current level of evidence, clinical applicability, and remaining challenges. A narrative review should provide interpretation rather than only description.

1. Methodology of the literature review should be strengthened.

The literature search is described only briefly. The authors should clearly explain how studies were selected, whether exclusion criteria were applied, how study quality was assessed, and how the final evidence was synthesized. Even for a narrative review, greater methodological transparency would improve scientific rigor.

1. Clinical applicability should be emphasized.

Many advanced technologies discussed (omics, AI, digital twins, multi-omics integration) remain primarily research tools. The manuscript would benefit from a more balanced discussion distinguishing technologies that are currently available for routine clinical use from those that remain experimental or require further validation.

1. The manuscript would benefit from improved organization.

Some chapters overlap considerably, particularly those discussing biomarkers, omics technologies, microbiome analysis, and predictive models. Several sections could be merged to avoid redundancy and improve logical flow.

Minor comments

1. Some references appear to be used repeatedly for similar statements throughout the manuscript. Consider reducing unnecessary citation duplication.
2. Several paragraphs contain very long sentences that should be shortened to improve readability.
3. Some tables summarize information already extensively discussed in the text. They could be simplified to improve clarity.
4. The English language is generally good but would benefit from careful professional editing to improve style and eliminate minor grammatical inconsistencies.
5. The conclusion should provide a more balanced perspective by emphasizing both the promise of emerging technologies and the barriers that currently limit their widespread implementation.

 

Author Response

Response to Reviewers

Dear Editor and Reviewers,

We sincerely thank the reviewers for their careful and constructive evaluation of our manuscript. The comments have substantially improved the clarity, rigor, and readability of the work. Below, we address each point individually; reviewer comments are in italics, and our responses follow. All changes are highlighted in the revised manuscript.

Reviewer 1

Comment 1. The methodology is the weakest part: no exact search string, MeSH terms, date of search, number of retrieved studies, inclusion/exclusion criteria, or study selection process.

We restructured the Materials and Methods into five subsections following the SANRA framework: Study Design and Reporting Framework (2.1), Data Sources and Search Strategy (2.2), Eligibility Criteria (2.3), Study Selection (2.4), and Quality Appraisal and Evidence Synthesis (2.5). We now report the databases searched (PubMed/MEDLINE, Scopus, Web of Science), the period covered (January 2015–December 2025), the last search-update date (20 January 2026), the combination of MeSH and free-text terms with Boolean operators, and representative search strings, together with explicit inclusion and exclusion criteria and the screening/selection process. We also added the number of records identified and screened at each stage to §2.4 The final synthesis included 66 references.

Comment 2. Insufficient discussion of biomarkers (reproducibility, external validation, sensitivity, heterogeneity) and limited discussion of therapeutic interventions (regenerative approaches, host modulation, biomaterials, minimally invasive surgery).

We expanded the critical discussion of biomarkers throughout Sections 3.5 and 5, explicitly addressing reproducibility, the frequent absence of external validation, reported sensitivity/specificity, and between-study heterogeneity, and clarifying that cross-sectional discrimination does not equate to validated prediction of activity or progression. Section 7 (Therapeutic Implications) was reorganized into dedicated subsections covering host- and microbiome-directed adjuncts (7.2), regeneration and minimally invasive surgery (7.3), and biomaterials and advanced delivery systems (7.4), each distinguishing clinically validated interventions from investigational ones.

Comment 3. Table 1 could be improved by adding evidence level, advantages/disadvantages, and limitations.

Table 1 was restructured to include, for each omics approach, columns for representative evidence, level of evidence, advantages, and limitations/disadvantages. The caption, the introductory sentence, and the table note were updated accordingly.

Comment 4. Minor: inconsistent subsection numbering (section 1 followed by 2.1); some abbreviations used before being defined; the introduction is very long.

Subsection numbering was made consistent throughout; in particular, the subsections of Section 7 were renumbered 7.1–7.5. Abbreviations are now defined at first use, including cone-beam computed tomography (CBCT), European Federation of Periodontology (EFP), and matrix metalloproteinase (MMP). The Introduction was condensed to focus on the rationale and aims of the review.

Reviewer 2

Comment 1. The manuscript lacks a clear structure for a narrative review; the SANRA checklist should be followed.

The manuscript was restructured according to SANRA (cited as reference 1), which now guides the justification of importance, the statement of aims, the description of the literature search, referencing, scientific reasoning, and the presentation of relevant data. This allowed us to trim the text and analyze the available data more critically.

Comment 2. The study is not easy to follow; data of the studies are not reported and not critically analyzed.

We revised the text to report quantitative findings (e.g., diagnostic AUCs, sensitivity/specificity) and to interpret rather than merely summarize them, consistently emphasizing validation status, heterogeneity, and clinical applicability across the diagnostic domains.

Comment 3. The data of the included studies should be presented as a table.

Study-level data are now presented in Table 1 (omics-based approaches) and Table 2 (biological-fluid biomarkers), each reporting representative evidence, performance, and limitations.

Comment 4. Adding figures would help present each section (e.g., a figure for CBCT, a figure for AI).

We added two new figures: Figure 2 (clinical indications and translational requirements of CBCT) and Figure 3 (biological fluids and biomarkers: scope, representative markers, and interpretation), complementing the existing Figure 1 on the roles of digital imaging and AI. Each is placed within the relevant section.

Comment 5. A graphical abstract needs to be added.

An original graphical abstract summarizing the transition from traditional concepts to precision periodontology has been added after the keywords and is provided as a separate file, prepared in accordance with MDPI's specifications.

Reviewer 3

Comment 1. The manuscript is excessively long and repetitive.

We condensed the text and removed redundant background, merging overlapping content (particularly across biomarkers, omics, microbiome, and predictive models) to reduce repetition while preserving the key scientific messages.

Comment 2. The review lacks sufficient critical analysis.

Throughout the revision, we shifted from description to interpretation, comparing the strengths and limitations of the different diagnostic technologies, their current level of evidence, clinical applicability, and remaining challenges. Table 1 now makes the level of evidence explicit.

Comment 3. The methodology of the literature review should be strengthened.

As detailed in our response to Reviewer 1 (Comment 1), the methodology now explains how studies were identified and selected, the eligibility criteria applied, how quality was appraised, and how the evidence was synthesized.

Comment 4. Clinical applicability should be emphasized; distinguish routine tools from experimental ones.

The revised text and tables consistently distinguish technologies currently available for routine clinical use from those that remain experimental or require further validation, and the added figures and graphical abstract reinforce this distinction (foundation vs. adjunct vs. investigational).

Comment 5. The manuscript would benefit from improved organization; some chapters overlap and could be merged.

Overlapping sections were consolidated and reordered to improve logical flow, following the thematic structure described in §2.5.

Minor comments. Repeated citations were reduced; long sentences were shortened; tables were revised to complement rather than duplicate the text; the English was professionally edited for style and consistency; and the Conclusions were rebalanced to present both the promise of emerging technologies and the barriers (validation, standardization, cost, and accessibility) that currently limit their routine implementation.

We believe these revisions address all the reviewers' concerns and hope the manuscript is now suitable for publication. We thank the reviewers again for their valuable input.

Sincerely,
The Authors

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The revised version is improved a lot after revisions. I have no further comments.

Reviewer 2 Report

Comments and Suggestions for Authors

NIL